Variant 20-3691423-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_023068.4(SIGLEC1):c.4508G>A(p.Arg1503His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000868 in 1,613,178 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

SIGLEC1
NM_023068.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.326

Variant links:

Genes affected

SIGLEC1 (HGNC:11127): (sialic acid binding Ig like lectin 1) This gene encodes a member of the immunoglobulin superfamily. The encoded protein is a lectin-like adhesion molecule that binds glycoconjugate ligands on cell surfaces in a sialic acid-dependent manner. It is a type I transmembrane protein expressed only by a subpopulation of macrophages and is involved in mediating cell-cell interactions. The protein plays an important role in multiple human diseases and bacterial and viral infections has been shown to enhance SARS-CoV-2 infection. [provided by RefSeq, Dec 2021]

SIGLEC1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SIGLEC1	NM_023068.4 linkuse as main transcript	c.4508G>A	p.Arg1503His	missense_variant	18/22	ENST00000344754.6
SIGLEC1	NM_001367089.1 linkuse as main transcript	c.4508G>A	p.Arg1503His	missense_variant	17/20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SIGLEC1	ENST00000344754.6 linkuse as main transcript	c.4508G>A	p.Arg1503His	missense_variant	18/22	1	NM_023068.4	P2	Q9BZZ2-1
SIGLEC1	ENST00000707083.1 linkuse as main transcript	c.4508G>A	p.Arg1503His	missense_variant	17/20			A2
SIGLEC1	ENST00000419548.4 linkuse as main transcript	c.950G>A	p.Arg317His	missense_variant	4/5	2

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152248

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000723

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000798

AC:

AN:

250532

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135694

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000885

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000684

AC:

AN:

1460930

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

726768

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000719

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152248

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74388

show subpopulations

Gnomad4 AFR

AF:

0.0000723

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 05, 2023

The c.4508G>A (p.R1503H) alteration is located in exon 17 (coding exon 17) of the SIGLEC1 gene. This alteration results from a G to A substitution at nucleotide position 4508, causing the arginine (R) at amino acid position 1503 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.32

Cadd

Uncertain

Dann

Pathogenic

1.0

DEOGEN2

Benign

0.23

Eigen

Uncertain

0.42

Eigen_PC

Uncertain

0.32

FATHMM_MKL

Benign

0.42

LIST_S2

Benign

0.69

M_CAP

Benign

0.033

MetaRNN

Uncertain

0.65

MetaSVM

Benign

-0.54

MutationAssessor

Pathogenic

3.0

MutationTaster

Benign

0.60

D;D

PrimateAI

Benign

0.45

PROVEAN

Benign

-2.1

REVEL

Benign

0.26

Sift

Benign

0.088

Sift4G

Uncertain

0.033

Polyphen

1.0

Vest4

0.34

MutPred

0.75

Loss of methylation at R1503 (P = 0.0532);

MVP

0.62

MPC

0.54

ClinPred

0.96

GERP RS

4.4

Varity_R

0.070

gMVP

0.26

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over